Exploring the Pharmacological Potential of Metformin for Neurodegenerative Diseases

Abstract

Metformin, one of the first-line of hypoglycemic drugs, has cardioprotective, anti-inflammatory and anticancer activities, in addition to its proven hypoglycemic effects. Furthermore, the preventive and therapeutic potential of metformin for neurodegenerative diseases has become a topic of concern. Increasing research suggests that metformin can prevent the progression of neurodegenerative diseases. In recent years, many studies have investigated the neuroprotective effect of metformin in the treatment of neurodegenerative diseases. It has been revealed that metformin can play a neuroprotective role by regulating energy metabolism, oxidative stress, inflammatory response and protein deposition of cells, and avoiding neuronal dysfunction and neuronal death. On the contrary, some have hypothesized that metformin has a two-sided effect which may accelerate the progression of neurodegenerative diseases. In this review, the results of animal experiments and clinical studies are reviewed to discuss the application prospects of metformin in neurodegenerative diseases.

Keywords: AMP-activated protein kinase; metformin; narrative review; neurodegeneration; pharmacology.

FIGURE 1

Mechanisms of metformin related to neuroprotection for NDD. The progression of neurodegenerative diseases has been shown to be associated with Tau phosphorylation, oxidative stress, amyloid protein accumulation and inflammation. Metformin can inhibit the NF-κB pathway, inhibit the astrocyte inflammation. In neurons, metformin directly inhibits Tau phosphorylation through PP2A. Most importantly, metformin inhibits respiratory chain complex 1, which inhibits energy production. This reduces ROS production, increases the AMP/ATP ratio, and then activates AMPK, which in turn inhibits Aβ plaque, protein synthesis, cell death and autophagy pathways. In general, metformin has great potential for neuroprotection based on current preclinical studies.